Liver NeoplasmsPhase 3GEMOXIALNCT00470340
Chemotherapy or Not, Following Complete Treatment of Hepatic Cancer in Cirrhotic Patients
A Phase 3 study testing Oxaliplatin, gemcitabine, cisplatin, lipiodol in people with Liver Neoplasms and Liver Cirrhosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Besides liver transplantation, the curative treatment of primary hepatic cancer with cirrhosis remains the surgical resection. Radiofrequency or cryotherapy currently allow local ablation of small cancer, with very good results. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular
- What is being tested?
- Oxaliplatin, gemcitabine, cisplatin, lipiodol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 263 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2007to Nov 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hepatocellular carcinoma (histology or Barcelona criteria) curatively treated by surgical resection or by radiofrequency or by cryotherapy
- Evidence of liver cirrhosis (clinical, biological, endoscopic or histological criteria)
- Morphological evaluation 4 to 6 weeks following curative treatment
- No evidence of local or distant disease on the morphological evaluation
- Absence of peritoneal or lymph node metastasis
- Absence of pre- or per-operative macroscopic tumoral thrombus
Show all 19Show fewer
- Minimal free margin of 5 mm following pathological exam
- ALPHAAFOETOPROTEINE level of less than 4 normal values or decreased by 50%, 4 to 6 weeks following curative treatment
- Biological criteria, 2 weeks before treatment as follow:
- neutrophilic polymorphonuclear > 1500/mm3,
- platelets > 100 000/mm3,
- total bilirubin < 25 mmol/l (1.46 mg/dl),
- creatinin < 1.5 x normal value
- Eastern Cooperative Oncology Group (ECOG) equal to 0 or 1
- Life expectancy > 12 weeks
- Absence of sensitive neuropathy at inclusion time
- Health insurance coverage
- Efficient contraceptive method if applicable
- Signed informed consent
Who cannot join
- Curative treatment performed 10 weeks or more before the beginning of adjuvant treatment
- Contraindication to an angiography or hepatic artery thrombosis or portal thrombosis.
- Pregnant or breastfeeding woman
- Concomitant involvement to any clinical trial
- Decompensate cirrhosis and Child-Pugh score ≥ 8 or clinical ascitis.
- Cancer of the Liver Italian Program (C.L.I.P.) score ≥ 2
Show all 16Show fewer
- Heart or lung insufficiency
- Other cancer not considered as definitively cured
- Creatinin clearance < 30 ml/min
- Recurrence of HCC less than 12 months following any last treatment
- Any radiotherapy during the 4 weeks before inclusion
- Known sensitivity to any drug of this protocol
- Immunodeficiency (HIV+, transplanted patient)
- Inability of follow up
- Impossibility of clear understanding of the protocol for no french speaking patient
- Patient under legal protection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Arterial LIPIODOLISED Chemotherapy Versus Systemic Chemotherapy With Gemcitabine Plus Oxaliplatin (GEMOX) Versus no Treatment Following Surgical Resection or Local Ablation of Hepatocellular Carcinoma in Cirrhotic Patients
Besides liver transplantation, the curative treatment of primary hepatic cancer with cirrhosis remains the surgical resection. Radiofrequency or cryotherapy currently allow local ablation of small cancer, with very good results. However, all these treatments are followed by high rates of recurrence (50 - 70% at 5 years). Then, it seems essential to associate to the surgical resection or to the local ablation as "adjuvant" treatment, in order to prevent or to decrease the rate of recurrence. However, no evidence supports this attitude. Therefore, following curative treatment of primary hepatic cancer with cirrhosis, we propose to compare treated to untreated patients. Postoperative treatment means either intra-arterial chemotherapy or systemic chemotherapy. The main criterion of the study is time of survival without recurrence. The main secondary objective is the safety.
Read the detailed description
The best treatment for hepatocellular carcinoma (HCC) with cirrhosis, currently is liver transplantation because treating the cancer and the causal disease. For the majority of patients, transplantation is not proposed, and the curative treatment remains the surgical resection. Radiofrequency or cryotherapy currently allows local destruction (or ablation) of the small HCC, with results that seem equivalent to the surgical resection. These last techniques increase the therapeutic possibilities in the presence of hepatic insufficiency. However, all these treatments are followed by high rates of recurrence (50 - 70% at 5 years and close to 100% at 10 years). The development of tumoral nodules, undetected at the time of the curative treatment, or the occurrence of new HCC, under the effects of the cirrhotic process or viral genomic modifications explain these disappointing results. Therefore, it seems essential to associate an adjuvant treatment to the surgical resection or the local destruction. Intra-arterial chemotherapy with or without embolisation is a largely evaluated therapeutic approach whose results are contradictory. Several retrospective studies, seem nevertheless to show a benefit of this treatment in adjuvant situation. Systemic chemotherapy for a long time regarded as ineffective, currently has a renewed interest due to the use of new drugs like gemcitabine and oxaliplatin (GEMOX regimen). This regimen showed a certain effect in a phase II study in advanced forms of HCC with cirrhosis. We propose to test by a prospective randomized multicentric phase III study, the effectiveness of an adjuvant treatment by systemic chemotherapy or intra-arterial LIPIODOLISED chemotherapy (CIAL), after surgery or complete local destruction of HCC. Three groups will be compared: a group of untreated patients (n=109), a group of patients treated by intra-arterial chemotherapy (CIAL = cisplatin 75 mg + lipiodol 10 ml; 3 courses every 6 weeks)(n=77) and a group of patients treated by systemic chemotherapy (GEMOX= day 1: gemcitabine 1000 mg/m² iv within 100 min; day 2: oxaliplatin 100 mg/m² iv within 2h; 8 courses every 2 weeks, d1 = d14)(n=77). Selection and randomisation are planned 4-8 weeks following complete treatment of the HCC. Identical follow up for the 3 groups includes clinical, biological, morphological exams every 3 months for 2 years, then every 6 months for 3 years. The main criterion of the study is survival without recurrence. The secondary objectives are the global survival, the safety and an estimate of the costs of the various treatments. The awaited results are 1) to demonstrate the effectiveness of at least one of these adjuvant treatment following complete treatment of HCC in cirrhotic patients and 2) to determine the best adjuvant treatment. Estimated inclusion time is 2 years, with an analysis of the principal criterion at 3 years. Follow-up of 5 years is envisaged for each patient, leading to a 7 years duration study.
- Conditions
- Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular, Recurrence, Neoplasm Recurrence, Local
- Being tested
- Oxaliplatin, gemcitabine, cisplatin, lipiodol
- Keywords
- Recurrence, Neoplasm Recurrence, Local, Liver, Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular, Iodized Oil, gemcitabine [Substance Name], oxaliplatin [Substance Name], gemcitabine-oxaliplatin regimen [Substance Name], Randomized Controlled Trials, Multicenter Studies, Cisplatin, Injections, Intra-Arterial, Injections, Intravenous, Chemotherapy, Adjuvant
- Medical subject headings
- Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular, Recurrence, Neoplasm Recurrence, Local
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxaliplatin, gemcitabine, cisplatin, lipiodolDrug
Oxaliplatin, gemcitabine, cisplatin, lipiodol
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Oxaliplatin, gemcitabine, cisplatin, lipiodol Receives: Drug: Oxaliplatin, gemcitabine, cisplatin, lipiodol |
| 2 | Experimental | Oxaliplatin, gemcitabine, cisplatin, lipiodol Receives: Drug: Oxaliplatin, gemcitabine, cisplatin, lipiodol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival without recurrence at 2 years
Measured: 2 years
Secondary outcomes (1)
Morbidity and mortality following adjuvant treatment
Measured: at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2007 (estimated)
- Study startJun 2007
- Primary completionNov 2008
- Study completionNov 2008
Why it stopped: during the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver NeoplasmsStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 263 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Investigators
- Eric Savier, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00470340
- Sponsor's protocol ID
- P051062
- Acronym
- GEMOXIAL
- Status last verified
- May 2007
- First submitted
- 4 May 2007
- Last updated
- 5 May 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Arterial LIPIODOLISED Chemotherapy Versus Systemic Chemotherapy With Gemcitabine Plus Oxaliplatin (GEMOX) Versus no Treatment Following Surgical Resection or Local Ablation of Hepatocellular Carcinoma in Cirrhotic Patients
- ClinicalTrials.gov ID
- NCT00470340
- Acronym / sponsor ID
- GEMOXIAL / P051062
- Conditions
- Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular, Recurrence, Neoplasm Recurrence, Local
- Keywords
- Recurrence, Neoplasm Recurrence, Local, Liver, Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular, Iodized Oil, gemcitabine [Substance Name]
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: during the study
- Enrolment
- 263 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 7 May 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Besides liver transplantation, the curative treatment of primary hepatic cancer with cirrhosis remains the surgical resection. Radiofrequency or cryotherapy currently allow local ablation of small cancer, with very good results. However, all these treatments are followed by high rates of recurrence (50 - 70% at 5 years). Then, it seems essential to associate to the surgical resection or to the local ablation as "adjuvant" treatment, in order to prevent or to decrease the rate of recurrence. However, no evidence supports this attitude. Therefore, following curative treatment of primary hepatic cancer with cirrhosis, we propose to compare treated to untreated patients. Postoperative treatment means either intra-arterial chemotherapy or systemic chemotherapy. The main criterion of the study is time of survival without recurrence. The main secondary objective is the safety.
Detailed description
The best treatment for hepatocellular carcinoma (HCC) with cirrhosis, currently is liver transplantation because treating the cancer and the causal disease. For the majority of patients, transplantation is not proposed, and the curative treatment remains the surgical resection. Radiofrequency or cryotherapy currently allows local destruction (or ablation) of the small HCC, with results that seem equivalent to the surgical resection. These last techniques increase the therapeutic possibilities in the presence of hepatic insufficiency. However, all these treatments are followed by high rates of recurrence (50 - 70% at 5 years and close to 100% at 10 years). The development of tumoral nodules, undetected at the time of the curative treatment, or the occurrence of new HCC, under the effects of the cirrhotic process or viral genomic modifications explain these disappointing results. Therefore, it seems essential to associate an adjuvant treatment to the surgical resection or the local destruction. Intra-arterial chemotherapy with or without embolisation is a largely evaluated therapeutic approach whose results are contradictory. Several retrospective studies, seem nevertheless to show a benefit of this treatment in adjuvant situation. Systemic chemotherapy for a long time regarded as ineffective, currently has a renewed interest due to the use of new drugs like gemcitabine and oxaliplatin (GEMOX regimen). This regimen showed a certain effect in a phase II study in advanced forms of HCC with cirrhosis. We propose to test by a prospective randomized multicentric phase III study, the effectiveness of an adjuvant treatment by systemic chemotherapy or intra-arterial LIPIODOLISED chemotherapy (CIAL), after surgery or complete local destruction of HCC. Three groups will be compared: a group of untreated patients (n=109), a group of patients treated by intra-arterial chemotherapy (CIAL = cisplatin 75 mg + lipiodol 10 ml; 3 courses every 6 weeks)(n=77) and a group of patients treated by systemic chemotherapy (GEMOX= day 1: gemcitabine 1000 mg/m² iv within 100 min; day 2: oxaliplatin 100 mg/m² iv within 2h; 8 courses every 2 weeks, d1 = d14)(n=77). Selection and randomisation are planned 4-8 weeks following complete treatment of the HCC. Identical follow up for the 3 groups includes clinical, biological, morphological exams every 3 months for 2 years, then every 6 months for 3 years. The main criterion of the study is survival without recurrence. The secondary objectives are the global survival, the safety and an estimate of the costs of the various treatments. The awaited results are 1) to demonstrate the effectiveness of at least one of these adjuvant treatment following complete treatment of HCC in cirrhotic patients and 2) to determine the best adjuvant treatment. Estimated inclusion time is 2 years, with an analysis of the principal criterion at 3 years. Follow-up of 5 years is envisaged for each patient, leading to a 7 years duration study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Oxaliplatin, gemcitabine, cisplatin, lipiodolOxaliplatin, gemcitabine, cisplatin, lipiodol |
| 2 | Experimental | Drug: Oxaliplatin, gemcitabine, cisplatin, lipiodolOxaliplatin, gemcitabine, cisplatin, lipiodol |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Hepatocellular carcinoma (histology or Barcelona criteria) curatively treated by surgical resection or by radiofrequency or by cryotherapy
- Evidence of liver cirrhosis (clinical, biological, endoscopic or histological criteria)
- Morphological evaluation 4 to 6 weeks following curative treatment
- No evidence of local or distant disease on the morphological evaluation
- Absence of peritoneal or lymph node metastasis
Key exclusion criteria (16 listed)
- Curative treatment performed 10 weeks or more before the beginning of adjuvant treatment
- Contraindication to an angiography or hepatic artery thrombosis or portal thrombosis.
- Pregnant or breastfeeding woman
- Concomitant involvement to any clinical trial
- Decompensate cirrhosis and Child-Pugh score ≥ 8 or clinical ascitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oxaliplatin, gemcitabine, cisplatin, lipiodolOxaliplatin, gemcitabine, cisplatin, lipiodol | Drug | 1, 2 |
Primary outcome
Survival without recurrence at 2 years
Time frame: 2 years
1 secondary outcome
Morbidity and mortality following adjuvant treatment
Time frame: at 6 months
Results and safety
The study was stopped early (reason given: during the study). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Savier, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oxaliplatin, gemcitabine, cisplatin, lipiodol in people with Liver Neoplasms and Liver Cirrhosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: during the study). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival without recurrence at 2 years (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2011.